scholarly journals Differential Effects of Serum Lipoprotein-Associated Phospholipase A2 on Periventricular and Deep Subcortical White Matter Hyperintensity in Brain

2021 ◽  
Vol 12 ◽  
Author(s):  
Junying Jiang ◽  
Yuanyuan Gao ◽  
Rui Zhang ◽  
Lin Wang ◽  
Xiaoyuan Zhao ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Atrial Fibrillation ◽  
Regression Analysis ◽  
White Matter ◽  
Phospholipase A2 ◽  
Elevated Serum ◽  
Advanced Age ◽  
Lacunar Infarction ◽  
White Matter Hyperintensity ◽  
Ordinal Regression Analysis

Background and Purpose: Serum level of lipoprotein-associated phospholipase A2 (Lp-PLA2) was associated with white matter hyperintensity (WMH). There were differences in the anatomical structure and pathophysiological mechanism between periventricular WMH (PVWMH) and deep subcortical WMH (DSWMH). In this study, we aimed to investigate the effects of serum Lp-PLA2 on the PVWMH and DSWMH.Methods: In total, 711 Chinese adults aged ≥45 years with cranial magnetic resonance imaging (MRI) were recruited in this cross-sectional study, who had received physical examinations in the Department of Neurology, the Affiliated Jiangning Hospital of Nanjing Medical University due to dizziness and headaches between January 2016 and July 2019. Enzyme linked immunosorbent assay (ELISA) was utilized to determine the serum Lp-PLA2. Fazekas scale was used to measure the severity of PVWMH (grade 0–3) and DSWMH (grade 0–3) on MRI scans. Ordinal regression analysis was carried out to investigate the relationship between serum Lp-PLA2 and PVWMH or DSWMH.Results: Finally, 567 cases were included in this study. The average level of serum Lp-PLA2 was 213.35±59.34 ng/ml. There were statistical differences in the age, hypertension, diabetes mellitus, atrial fibrillation, lacunar infarction, Lp-PLA2 grade, creatinine, Hcy, and H-CRP (P < 0.05) in PVWMH groups. Ordinal regression analysis indicated that there was a lower risk of PVWMH in the patients with normal and moderately elevated serum Lp-PLA2 compared with those with significantly elevated serum Lp-PLA2 after adjusting age, hypertension, diabetes mellitus, atrial fibrillation, lacunar infarction, Cr, Hcy, and H-CRP. In addition, PVWMH was correlated to advanced age, hypertension, diabetes mellitus, and lacunar infarction. After adjusting for confounding factors, DSWMH was correlated to advanced age and lacunar infarction. There was no correlation between serum Lp-PLA2 and DSWMH.Conclusions: Serum Lp-PLA2 was closely associated with the pathogenesis of PVWMH rather than DSWMH. There might be different pathological mechanisms between PVWMH and DSWMH.

scholarly journals Differential effects of serum lipoprotein-associated phospholipase A2 on periventricular and deep subcortical white matter hyperintensity in brain

2020 ◽  
Author(s):  
Junying Jiang ◽  
Yuanyuan Gao ◽  
Rui Zhang ◽  
Lin Wang ◽  
Xiaoyuan Zhao ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
White Matter ◽  
Phospholipase A2 ◽  
Logistic Regression Analysis ◽  
Elevated Serum ◽  
Ordinal Logistic Regression ◽  
Lacunar Infarction ◽  
White Matter Hyperintensity ◽  
Ordinal Logistic Regression Analysis

Abstract Background: High lipoprotein-associated phospholipase A2 (Lp-PLA2) was associated with white matter hyperintensity (WMH). There were differences in the anatomical structure and pathophysiological mechanism between periventricular WMH (PVWMH) and deep subcortical WMH (DSWMH). In this study, we aimed to investigate the effects of serum Lp-PLA2 on the PVWMH and DSWMH. Methods: This cross-sectional study recruited 711 Chinese adults aged ≥45 years presented to the Department of Neurology, the Affiliated Jiangning Hospital of Nanjing Medical University between January 2016 and July 2019. Enzyme linked immunosorbent assay (ELISA) was utilized to determine the serum Lp-PLA2. Fazekas scale was used to measure the severity of PVWMH and DSWMH. Ordinal logistic regression analysis was carried out to investigate the relationship between serum Lp-PLA2 and PVWMH or DSWMH. Results: A total of 567 cases were included in this study. Ordinal logistic regression analysis indicated that, after adjusting for the confounding variables, there was a lower risk of PVWMH in the patients with normal and moderately elevated serum Lp-PLA2 compared with those with significantly elevated serum Lp-PLA2. In addition, PVWMH was correlated to advanced age, hypertension, diabetes mellitus, and lacunar infarction. DSWMH was correlated to advanced age and lacunar infarction. There was no correlation between serum Lp-PLA2 and DSWMH. Conclusions: Serum Lp-PLA2 was closely associated with the pathogenesis of PVWMH rather than DSWMH. There might be different pathological mechanisms between PVWMH and DSWMH.

Abstract 44: Associations of Atrial Fibrillation, Neuroimaging Measures of Cerebrovascular Disease and Alzheimer’S Disease-related Pathology, and Cognitive Impairment

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Jonathan Graff-Radford ◽  
Rosebud Roberts ◽  
Malini Madhavan ◽  
Alejandro Rabinstein ◽  
Ruth Cha ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
White Matter ◽  
Cerebrovascular Disease ◽  
Regression Models ◽  
Grey Matter ◽  
White Matter Hyperintensity ◽  
Carrier Status

The objective of this study was to investigate the cross-sectional associations of atrial fibrillation with neuroimaging measures of cerebrovascular disease and Alzheimer’s disease-related pathology, and their interaction with cognitive impairment. MRI scans of non-demented individuals (n=1044) from the population-based Mayo Clinic Study of Aging were analyzed for infarctions, total grey matter, hippocampal and white matter hyperintensity volumes. A subset of 496 individuals underwent FDG and C-11 Pittsburgh compound B (PiB) PET scans. We assessed the associations of atrial fibrillation with i) categorical MRI measures (cortical and subcortical infarctions) using multivariable logistic regression models, and with ii) continuous MRI measures ( hippocampal, total grey matter, and white matter hyperintensity volumes) and FDG-PET and PiB-PET measures using multivariable linear regression models, and adjusting for confounders. Among participants who underwent MRI (median age, 77.8, 51.6% male), 13.5% had atrial fibrillation. Presence of atrial fibrillation was associated with subcortical infarctions (odds ratio [OR], 1.83; p=0.002), cortical infarctions (OR, 1.91; p=0.03), total grey matter volume (Beta [β], -.025, p<.0001) after controlling for age, education, gender, APOE e4 carrier status, coronary artery disease, diabetes, history of clinical stroke, and hypertension. However, atrial fibrillation was not associated with white matter hyperintensity volume, hippocampal volume, Alzheimer’s pattern of FDG hypometabolism or PiB uptake. There was a significant interaction of cortical infarction (p for interaction=0.004) and subcortical infarction (p for interaction =0.015) with atrial fibrillation with regards to odds of mild cognitive impairment (MCI). Using subjects with no atrial fibrillation and no infarction as the reference, the OR (95% confidence intervals [CI]) for MCI was 2.98 (1.66, 5.35;p = 0.0002) among participants with atrial fibrillation and any infarction, 0.69 (0.36, 1.33;p= 0.27) for atrial fibrillation and no infarction, and 1.50 (0.96, 2.32;p = 0.07) for no atrial fibrillation and any infarction. These data highlight that atrial fibrillation is associated with MCI in the presence of infarctions.

scholarly journals Genetically predicted levels of the human plasma proteome and risk of stroke: a Mendelian Randomization study

2021 ◽  
Author(s):  
Lingyan Chen ◽  
James Peters ◽  
Bram Prins ◽  
Elodie Persyn ◽  
Matthew Traylor ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Body Mass Index ◽  
White Matter ◽  
Body Mass ◽  
White Matter Hyperintensity ◽  
Mendelian Randomisation ◽  
Beneficial Effects ◽  
Causal Pathways

Abstract Proteins are the effector molecules of biology and are the target of most drugs. To identify proteins and related pathways that may play a causal role in stroke pathogenesis, we used Mendelian randomisation (MR). We tested potential causal effects of 308 plasma proteins (measured in 4,994 blood donors from the INTERVAL study) on stroke outcomes (derived from the MEGASTROKE GWAS) in a two-sample MR framework and assessed whether these associations could be mediated by cardiovascular risk factors. We extended the analysis to identify whether pharmacological targeting of these proteins might have potential adverse side-effects or beneficial effects for other conditions through Phenome-wide MR (Phe-MR) in UK Biobank. MR showed an association between stroke and genetically predicted plasma levels of TFPI, IL6RA, MMP12, CD40, TMPRSS5 and CD6 (P≤1.62⋅10−4). We identified six risk factors (atrial fibrillation, body mass index, smoking, blood pressure, white matter hyperintensities and type 2 diabetes) that were associated with stroke (P≤0.0071) using MR. The association of TFPI, IL6RA and TMPRSS5 with stroke could be mediated by these risk factors, such as body mass index, white matter hyperintensity and atrial fibrillation. Thirty-six additional proteins were potentially causal for one or more of these risk factors. The Phe-MR suggested that targeting TFPI could have potential beneficial effects on other disorders of arteries and hyperlipidaemia in addition to stroke. Our results highlight novel causal pathways and potential therapeutic targets for stroke.

Abstract TMP58: Determinants of White Matter Hyperintensity in Acute Ischemic Stroke Patients: The MRI-GENIE Study

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Anne-Katrin Giese ◽  
Markus D Schirmer ◽  
Adrian V Dalca ◽  
Ramesh Sridharan ◽  
Lisa Cloonan ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Ischemic Stroke ◽  
White Matter ◽  
Stroke Risk ◽  
Smoking Status ◽  
Vascular Risk Factors ◽  
White Matter Hyperintensity ◽  
Vascular Risk ◽  
Prior Stroke

Introduction: White matter hyperintensity (WMH) is a highly heritable trait and a significant contributor to stroke risk and severity. Vascular risk factors contribute to WMH severity; however, knowledge of the determinants of WMH in acute ischemic stroke (AIS) is still limited. Hypothesis: WMH volume (WMHv) varies across AIS subtypes and is modified by vascular risk factors. Methods: We extracted WMHv from the clinical MRI scans of 2683 AIS subjects from the MRI-Genetics Interface Exploration (MRI-GENIE) study using a novel fully-automated, volumetric analysis pipeline. Demographic data, stroke risk factors and stroke subtyping for the Causative Classification of Stroke (CCS) were performed at each of the 12 international study sites. WMHv was natural log-transformed for linear regression analyses. Results: Median WMHv was 5.7cm 3 (interquartile range (IQR): 2.2-12.8cm 3 ). In univariable analysis, age (63.1 ± 14.7 years, β=0.04, SE=0.002), prior stroke (10.2%, β=0.66, SE=0.08), hypertension (65.4%, β=0.75, SE=0.05), diabetes mellitus (23.1%, β=0.35, SE=0.06), coronary artery disease (17.6%, β=0.04, SE=0.002), and atrial fibrillation (14.6%, β=0.48, SE=0.07) were significant predictors of WMHv (all p<0.0001), as well as smoking status (52.2%, β=0.15, SE=0.05, p=0.005), race (16.5% Non-Caucasian, β=0.25, SE=0.07) and ethnicity (8.2% Hispanic, β=0.30, SE=0.11) (all p<0.01). In multivariable analysis, age (β=0.04, SE=0.002), prior stroke (β=0.56, SE=0.08), hypertension (β=0.33, SE=0.05), smoking status (β=0.16, SE=0.05), race (β=0.42, SE=0.06), and ethnicity (β=0.34, SE=0.09) were independent predictors of WMHv (all p<0.0001), as well as diabetes mellitus (β=0.13, SE=0.06, p=0.02). WMHv differed significantly (p<0.0001, unadjusted) across CCS stroke subtypes: cardioembolic stroke (8.0cm 3 , IQR: 4.2-15.4cm 3 ), large-artery stroke (6.9cm 3 , IQR: 3.1-14.7cm 3 ), small-vessel stroke (5.8cm 3 , IQR: 2.5-13.5cm 3 ), stroke of undetermined (4.7cm 3 , IQR: 1.6-11.0cm 3 ) or other (2.55cm 3 , IQR: 0.9-8.8cm 3 ) causes. Conclusion: In this largest-to-date, multicenter hospital-based cohort of AIS patients with automated WMHv analysis, common vascular risk factors contribute significantly to WMH burden and WMHv varies by CCS subtype.

Serum CA 19–9 Level is Correlated to the Clinical Characteristics and Chronic Complications of Patients Newly Diagnosed with Type 2 Diabetes Mellitus

2019 ◽  
Author(s):  
Limei Cui ◽  
Naqiang Lv ◽  
Bin Li ◽  
Jing Tao ◽  
Xiaomin Zheng ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Regression Analysis ◽  
Clinical Characteristics ◽  
Elevated Serum ◽  
Newly Diagnosed ◽  
Chronic Complications

Abstract Aim This study investigated the relation of serum carbohydrate antigen 199 (CA 19–9) levels to the clinical characteristics and chronic complications of patients newly diagnosed with type 2 diabetes mellitus (T2DM). Methods A total of 371 patients newly diagnosed with T2DM and 133 healthy people with consecutively matched age were compared. The 371 patients with T2DM were divided into four groups by quartiles based on their serum CA 19–9 levels, in which clinical characteristics and chronic complications, such as diabetic retinopathy (DR), diabetic nephropathy, and macrovascular complications were compared. Logistic regression analysis was used to evaluate the risk factors of DR. Results Among the 371 patients newly diagnosed with T2DM, 60 had elevated CA 19–9 levels (16.17%). The frequencies of elevated serum CA 19–9 were 24.39% (30 of 123) for females and 12.10% (30 of 248) for males, in which the values for females were higher than those for males (P<0.01).Differences were observed among the serum CA 19–9 levels, hemoglobin A1c (HbA1c), and DR (P<0.05). Logistic regression analysis showed that serum CA 19–9 levels, fasting blood glucose (FBG) and fasting C-peptide (FC-P) were risk factors for DR (P<0.05). Conclusions Serum CA 19–9 levels were correlated with HbA1c and DR in patients newly diagnosed with T2DM. The elevated serum CA 19–9 levels, high FC-P, and FBG levels were important risk factors for DR in patients newly diagnosed with T2DM.

scholarly journals Hemispheric Asymmetry of White Matter Hyperintensity in Association With Lacunar Infarction

2018 ◽  
Vol 7 (22) ◽  
Author(s):  
Wi‐Sun Ryu ◽  
Dawid Schellingerhout ◽  
Hee‐Seung Ahn ◽  
Soo‐Hyun Park ◽  
Keun‐Sik Hong ◽  
...  
Keyword(s):  
White Matter ◽  
Hemispheric Asymmetry ◽  
Lacunar Infarction ◽  
White Matter Hyperintensity

scholarly journals CHA2DS2-VASc score, cerebral small vessel disease, and frailty in older patients with atrial fibrillation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jung-Yeon Choi ◽  
Leonard Sunwoo ◽  
Sun-wook Kim ◽  
Kwang-il Kim ◽  
Cheol-Ho Kim
Keyword(s):  
Atrial Fibrillation ◽  
White Matter ◽  
High Risk ◽  
Gait Speed ◽  
Structural Changes ◽  
Brain Volume ◽  
Frailty Index ◽  
Brain Magnetic Resonance Imaging ◽  
White Matter Hyperintensity ◽  
Physical Frailty

Abstract The CHA2DS2-VASc score is a validated predictor of ischemic stroke in atrial fibrillation (AF) patients. However, data are limited on whether the CHA2DS2-VASc score is associated with subclinical brain structural changes or physical frailty among older AF patients. We assessed the relationship between CHA2DS2-VASc scores and brain structural changes or physical frailty in AF patients without history of stroke. Overall, 117 patients completed a comprehensive geriatric assessment for physical frailty. In brain magnetic resonance imaging sub-study (n = 49), brain volume and white matter hyperintensity lesion burden were automatically quantified using the LESIONQUANT software program. Patients with high risk of CHA2DS2-VASc scores (≥ 2 in men or ≥ 3 in women) tended to be older and had more comorbidities, higher frailty index, and slower gait speed. Total white matter hyperintensity lesion burden was higher in those with high risk of CHA2DS2-VASc score than in those with intermediate risk (score of 1 in men or 2 in women) of CHA2DS2-VASc score (1.67 [interquartile range: 0.70–3.45] vs. 0.64 [0.19–1.44], p = 0.036). Cognitive function was associated with brain volume, but gait speed was related with white matter hyperintensity lesion burden. In conclusion, we showed a positive relationship between CHA2DS2-VASc scores, white matter hyperintensity lesion burden, and physical frailty in older AF patients. Subclinical brain changes associated with high CHA2DS2-VASc scores may predict physical frailty risk.

scholarly journals Neuropathologic basis of white matter hyperintensity accumulation with advanced age

Neurology ◽  
2013 ◽  
Vol 81 (11) ◽  
pp. 977-983 ◽  
Author(s):  
D. Erten-Lyons ◽  
R. Woltjer ◽  
J. Kaye ◽  
N. Mattek ◽  
H. H. Dodge ◽  
...  
Keyword(s):  
White Matter ◽  
Advanced Age ◽  
White Matter Hyperintensity
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